The proposed study aims at deepening our understanding of the effect of interactions of different malaria species on incidence of malarial infections, and resulting morbidity by conducting a longitudinal follow-up study of children 1 - 4 years of age in a holoendemic are of Papua New Guinea. In particular we will determine patterns of acute simple malaria and anemia associated with prior and concurrent infections of different Plasmodium species and ascertain cross-species protection malarial morbidity and anemia test the hypothesis that co-infections with P. vivax and/or P. malariae reduce the incidence and severity of clinical disease with concurrent or subsequent P. falciparum infections. We will also assess potential interactions at the levels of asymptomatic infections. Better knowledge of potential cross-species protection is crucial to understanding the epidemiology of malarial morbidity and the possible effects of interventions, such as a malaria vaccine, primarily directed at one of the species. In order to achieve those aims we will follow-up 250 children with bi-monthly bleeds, fortnightly active morbidity surveillance and passive case detection at local health centers. All blood samples from cross-sectional bleeds and detected morbid episodes will be evaluated for malarial infections with both light microscopy and PCR-ligase detection reaction (LDR) assay. At the same time hemoglobin levels will be determined. Cross-species protection against morbidity and associations between heterologous infections will be analyzed with a mixture of standard methods for cohort studies and innovative approaches including mixed models and generalized estimating equations (GEE). The combination of a powerful longitudinal design, the best available methods of species identifications and sophisticated statistical analyses offers a unique opportunity for an in-depth examination of all aspects of cross-species interactions in the same individuals and thereby help to resolve this important aspect of malaria epidemiology. [unreadable] [unreadable]